Predicting Sequence-Dependent Solubility Using Polymer Field Theory

Polymer synthesis has become increasingly sophisticated, enabling the creation of precise sequence-controlled polymers with tailored properties. However, the vast number of potential sequences demands robust and efficient modeling to predict how sequence impacts macromolecular interactions. In this work, we leverage sequence-specific peptoids as a platform to develop design rules linking chemical sequences to polymer solubility. We present a multiscale peptoid simulation workflow using small-scale, atomistic simulations to parameterize field-theoretic models. We use this workflow to predict solubility as a function of polymer sequence. Our results demonstrate that polymer sequence influences solubility—an effect often neglected in traditional polymer physics models, which typically only consider the impact of monomer type and composition. These findings expand our understanding of sequence-dependent behavior in polymers and offer new strategies for using sequence to design materials with tailored solubility and performance.